The susceptibility of adults who have family members with type 2 diabetes (DM) to the disease is markedly increased in the setting of sedentary living and excessive weight gain. Lifestyle modification combining modest weight loss and increased physical activity can reduce the incidence of DM in high-risk populations. Today, a growing number of Americans report having short sleep hours and prospective epidemiological data reveal an independent association of reduced sleep duration with an increased incidence of diabetes and obesity. It has been proposed that increased rates of energy metabolism require increased amounts of sleep to correct the biochemical consequences of waking metabolic activity. So far, the possibility that short sleep hours may compromise physical activity and its metabolic benefits, and exacerbate the adverse effects of sedentary living has not been considered. Thus, the primary goal of this proposal is to test the hypothesis that short sleep duration is accompanied by reduced levels of everyday physical activity and aerobic fitness, and that recurrent sleep loss can disrupt the maintenance of adequate levels of exercise in adults with increased risk for DM. Experimental sleep deprivation can also interfere with the secretion and systemic action of insulin in the absence of changes in everyday physical activity. However, the effects of recurrent sleep loss on the secretion and metabolic actions of insulin in high-risk populations have not been investigated. Another important goal of this proposal is to determine the magnitude and define the potential mechanisms of the effects of sleep loss on glucose homeostasis in adults at risk for DM. To achieve these goals, we will combine studies of high-risk individuals with established long-term differences in usual sleep duration under free-living conditions with experiments, that involve controlled manipulations of the amount of sleep in the laboratory, in order to explore the impact of short sleep hours on daily activity-related energy expenditure, exercise habits, beta-cell function, and insulin sensitivity in muscle, liver, and fat. If short sleep is found to have an adverse impact on the amount of physical activity-related energy expenditure, aerobic fitness, and insulin secretion or action in individuals at risk, these studies may help us to identify new non-pharmacological opportunities for the prevention of DM. PUBLIC HEALTH RELEVANCE: If short sleep is found to have an adverse impact on the amount of physical activity-related energy expenditure, aerobic fitness, and insulin secretion or action in individuals at risk, these studies may help us to identify new non-pharmacological opportunities for the prevention of DM.